[unreadable] The aim of this project is to better understand and thus to improve cerebral protection during surgery on the ascending aorta and aortic arch. At present, strokes and cognitive dysfunction after operations on aneurysms of the ascending aorta/arch are frequent and often serious complications, making patients hesitate to undergo elective operation. If cerebral protection were better, fewer patients with known aneurysms would die of rupture, or of complications from emergency surgery, which has a much higher mortality and morbidity. Of the methods currently used for cerebral protection, hypothermic circulatory arrest (HCA) is the simplest and best studied. But over the years--in part as the result of data emerging from this grant-- it has become apparent that durations of HCA > 30 minutes are associated with lasting cognitive impairment in a significant proportion of patients, and many operations cannot reliably be completed within such a short safe interval. Selective antegrade cerebral perfusion (SCP) is an alternative which allows continued flow to the brain during the aortic repair. SCP poses a greater risk of embolization than HCA, but allows almost unlimited time for completion of the operation. In contrast to HCA, however, its physiology has not been explored: whether SCP should be instituted following a brief interval of HCA; what are the ideal temperature, pressure, and hematocrit, and whether pharmacological strategies can improve its safety. We propose to study these questions using a clinically relevant chronic porcine model in which we can study blood flow and metabolism using fluorescent microspheres; evaluate electrophysiological recovery, behavioral outcome and ability to learn (using amaze), and assess subtle changes in neuronal morphology. With this well-established survival model, our multidisciplinary team-- comprising cardiothoracic Surgeons specializing in aneurysms, a neuropathologist with expertise in cognitive dysfunction, a neurophysiologist, and a biomathematician-- should be able to interpret the proposed experiments to improve our understanding of hypothermic cerebral protection. Many of the experiments will translate readily into changes in clinical implementation of strategies for cerebral protection, resulting in better patient outcomes. [unreadable] [unreadable]